FDA Alerts

FDA Actos News Release

Manufacturers of Some Diabetes Drugs to Strengthen Warning on Heart Failure Risk; Companies Will Include Boxed Warning on Drug Label

August 14, 2007 - The U.S. Food and Drug Administration today announced manufacturers of certain drugs approved to treat Type 2 diabetes have agreed to add a stronger warning on the risk of heart failure, a condition that occurs when the heart does not adequately pump blood. The information will be included in the form of a "boxed" warning — FDA's strongest form of a warning. The upgraded warning emphasizes that the drugs may cause or worsen heart failure in certain patients.

After a review of postmarketing adverse event reports, FDA determined that an updated label with a boxed warning on the risks of heart failure was needed for the entire thiazolidinedione class of antidiabetic drugs. This class includes Avandia (rosiglitazone), Actos (pioglitazone) Avandaryl (rosiglitazone and glimepiride), Avandamet (rosiglitazone and metformin), and Duetact (pioglitazone and glimepiride). These drugs are used in conjunction with diet and exercise, to improve blood sugar control in adults with type 2 (non-insulin-dependent) diabetes. FDA had asked the drug's manufacturers, GlaxoSmithKline and Takeda, to address these concerns.

"Under FDA's postmarketing surveillance program, we carefully monitor new safety information for marketed drugs and take appropriate action when necessary to inform patients and health care providers of new information," said Steven Galson, M.D., M.P.H., director of FDA's Center for Drug Evaluation and Research. "This new boxed warning addresses FDA's concerns that despite the warnings and information already listed in the drug labels, these drugs are still being prescribed to patients without careful monitoring for signs of heart failure."

FDA's review of adverse event reports found cases of significant weight gain and edema — warning signs of heart failure. In some reports, FDA noted, continuation of therapy has been associated with poor outcomes, including death.

The strengthened warning advises health care professionals to observe patients carefully for the signs and symptoms of heart failure, including excessive, rapid weight gain, shortness of breath, and edema after starting drug therapy. Patients with these symptoms who then develop heart failure should receive appropriate management of the heart failure and use of the drug should be reconsidered. People who have questions should contact their health care providers to discuss alternative treatments.

The warning also states that these drugs should not be used by people with serious or severe heart failure who have marked limits on their activity and who are comfortable only at rest or who are confined to bed or a chair.

FDA's review of Avandia and possible increased risk of heart attacks is ongoing. On July 30, 2007, FDA's Endocrine and Metabolic Advisory Committee and the Drug Safety and Risk Management Advisory Committee recommended that Avandia continue to be marketed, and further recommended that information be added to the labeling for risk of heart attacks (ischemic risks).


ACTOS FDA Alert
Pioglitazone HCl (marketed as Actos, Actoplus Met, and Duetact) Information

August, 2007:  FDA ALERT [8/2007]
This Alert highlights important revisions to the full prescribing information for pioglitazone HCl, marketed as Actos, Actoplus Met, and Duetact. The updated information includes a new BOXED WARNING, and additional updated WARNINGS, PRECAUTIONS and CONTRAINDICATIONS to emphasize that pioglitazone may cause or exacerbate heart failure, particularly in certain patient populations. The implications of this new labeling for healthcare professionals who prescribe Actos are summarized below. This information reflects FDA’s current analysis of data available to FDA concerning this drug. FDA intends to update this sheet when additional information or analyses become available. 

Pioglitazone is a thiazolidinedione (TZD) approved as an oral antidiabetic agent.  TZDs are selective ligands of the nuclear transcription factor peroxisome-proliferator-activator-receptor- γ (PPAR-γ) which improve glycemic control by increasing insulin sensitivity.  Three products, all manufactured by Takeda, contain pioglitazone:  Actos (pioglitazone) Actoplus Met (pioglitazone and metformin) and Duetact (pioglitazone and glimepiride).  Fluid retention, weight gain, edema, and heart failure are known side-effects of TZDs.  Continued post-marketing reports of heart failure have prompted the FDA to increase the prominence of this safety concern in the labels for these drugs.

Recommendations and Considerations

• Thiazolidinediones, including Actos, Actoplus Met, and Duetact, may cause or exacerbate congestive heart failure in some patients.

• Initiation of these drugs in patients with established NYHA Class III or IV heart failure is contraindicated.

• After initiation of Actos, Actoplus Met, and Duetact, and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain, dyspnea, and/or edema). 

• If these signs and symptoms develop and heart failure is confirmed, appropriate management of heart failure should be initiated.  Discontinuation or dose reduction of Actos, Actoplus Met, or Duetact should be considered.
Information for the Patient

• Patients should be informed that Actos, alone or in combination with other antidiabetic agents, can cause fluid retention, which may exacerbate or lead to heart failure. 

• Patients should be asked to watch for and report to their healthcare professional any signs and symptoms of heart failure, including edema from fluid retention, shortness of breath or trouble breathing, unusually fast increase in weight, and unusual tiredness.
Clinical Trial Data

In a 24-week study comparing Actos (n=262) to glyburide (n=256) in patients with NYHA Class II and III heart failure and ejection fraction less than 40% (mean EF 30% at baseline), overnight hospitalization for congestive heart failure was reported in 9.9% of patients on Actos compared to 4.7% of patients on glyburide.  This adverse event was more marked in patients using insulin at baseline and in patients over 64 years of age.

In a long-term cardiovascular outcomes trial, 5238 patients were randomized to Actos (n=2605) or placebo (n=2633) in addition to their background anti-diabetic medications. The average duration of follow-up was 34.5 months. There was no statistically significant difference between the two treatment groups for the primary composite endpoint of all-cause mortality, nonfatal MI, stroke, acute coronary syndrome, cardiac revascularization, major leg amputation, or leg revascularization. The percentage of patients who had a serious heart failure event was higher for patients treated with Actos (5.7%, n=149) than for patients treated with placebo (4.1%, n=108). The incidence of death subsequent to a report of heart failure was 1.5% (n=40) in patients treated with Actos and 1.4% (n=37) in placebo-treated patients. In patients treated with an insulin-containing regimen at baseline, the incidence of serious heart failure was 6.3% (n=54/864) with Actos and 5.2% (n=47/896) with placebo. For those patients treated with a sulfonylurea-containing regimen at baseline, the incidence of serious heart failure was 5.8% (n=94/1624) with Actos and 4.4% (n=71/1626) with placebo.

Next Steps
Healthcare professionals should factor this new labeling information into their individual treatment decisions for their patients.  FDA will continue to monitor post-marketing reports of heart failure and will analyze any additional studies for this, as well as other important adverse effects.  The agency will consider further regulatory action and communication as additional information becomes available.


Verdicts & Settlements

Scott has been involved in numerous and diverse settlements and verdicts throughout his 18 year legal career.  He prides himself on taking care of the injured people he represents.  Scott has represented individuals from almost every state in the country and can point to settlements involving millions of dollars. Whether it be a faulty medical device, a flawed manufacturing process, a failed prescription drug or some other issue that has caused personal injury, Scott has the experience, determination and the integrity to represent a client’s interests aggressively and see that justice is served. The following examples are but a few of recent notable accomplishments:

  • Hundreds of Scott’s clients from numerous states received monetary awards in the Silicone breast implant litigation. These cases involved defective leaking or ruptured silicone implants which caused significant injury, illness and/or damage to women who relied on the manufactures of the implants.  Scott worked with the women all the way through to verdict or settlement and was responsible for ultimately settling client cases for millions of dollars.

  • Scott represented clients in the Rezulin litigation which involved a drug used by diabetics. The FDA ultimately removed the drug from the market due to liver and cardiac adverse events. Scott was involved in hundreds of hours of document review and depositions in the U.S. and Europe.  He deposed corporate witnesses who designed, manufactured, marketed and sold the drug and his clients received exceptional settlements.

  • Scott and his partner Ed Blizzard were involved in representing hundreds of individuals who suffered as a result of defective Sulzer hip and knee implant replacement joints.  Scott and Ed worked at both the state and federal level and were instrumental in developing documents and deposing corporate witnesses so that ultimately a global settlement of all claims was announced.  Scott and Ed were able to secure millions in settlement for their clients.

  • Scott represented many clients who encountered problems as a result of the diet drugs Pondimin and Redux.  He was involved with discovery committees, reviewed thousands of documents and deposed many corporate witnesses.  He tried many of these cases to verdict receiving large settlements for his clients. In December 2000, Scott tried a case in Philadelphia for two ladies from Utah who developed heart valve damage after taking the diet drug combination known as Fen-Phen. After a two week trial the jury awarded each of his clients $100 million dollars. This $200 million dollar verdict stands today as the largest Fen-Phen valvular heart disease verdict in the country. Because of this verdict, Scott was inducted into the Million Dollar and the Multi-Million Dollar Advocates Forum.

  • Scott’s clients in the Ephedra litigation were compensated well for the damages they suffered.  These cases involved  products such as Herbalife, Dexatrim, Stacker and Hydroxicut that were associated with heart attacks and strokes. He was heavily involved in developing justification documents and taking corporate depositions that ultimately led to large dollar settlements for his clients.  

Most recently, Scott began working on Paxil birth defect cases. Paxil is an antidepressant still used by millions of Americans daily.  In recent years, however, it has been associated with significant heart defects when ingested by women during the first trimester of a pregnancy.  Scott has been actively prosecuting these cases against GSK, maker of the drug. One of his cases was the first to be set for trial.  The case was resolved in favor of Scott’s client.

Name
Comment
Phone
Email

Current Litigation:

Celexa
  • Heart Defects
  • Lung Defects

Zoloft
  • Heart Defects
  • Lung Defects

Prozac
  • Heart Defects
  • Lung Defects

DARVON & DARVOCET
  • Heart Rhythm

PAXIL
  • Birth Defects

REGLAN
  • Tardive Dyskinesia
  • Tardive Dystonia

ACCUTANE

ACTOS

DEPAKOTE

DePuy

MERIDIA

WELLBUTRIN

On the Web:



Office Location:

Lyric Centre
440 Louisiana, Suite 1710
Houston TX 77002-1689
our toll free # 800-349-0127
phone # 713-844-3750
fax # 713-844-3755

Visit us on Facebook
Visit us on Twitter

Map | Email Us


* Verdicts and settlement amount does not reflect client portion

Blizzard, McCarthy & Nabers, LLP represents clients in mass tort and primary pulmonary hypertension lawsuits nationwide, including Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Vermont, Virginia, Washington, West Virginia, Wisconsin and Wyoming.

We also serve the cities of New York, Los Angeles, Chicago, Houston, Phoenix, Philadelphia, San Antonio, San Diego, Dallas, San Jose City, Detroit, Jacksonville, Indianapolis, San Francisco, Columbus, Austin, Memphis, Fort Worth, Baltimore, Charlotte, Boston, Seattle, Washington, Milwaukee, Denver, Louisville, Las Vegas, Nashville, Oklahoma City, Portland, Tucson, Albuquerque, Atlanta, Long Beach, Fresno, Sacramento, Mesa, Kansas City, Cleveland, Virginia Beach, Omaha, Miami, Oakland, Tulsa, Honolulu, Minneapolis, Colorado Springs, Arlington and Wichita.